Multicenter prospective study of selinexor combined with azacitidine or ruxolitinib in patients with MDS/MPNs

Outcomes of treatments for myelodysplastic syndrome/myeloproliferative neoplasms (MDS/MPNs) are suboptimal. Selinexor, an oral selective inhibitor of exportin 1, represents a mechanism-based therapeutic approach. A multicenter prospective study in China evaluated selinexor plus either azacitidine (for MDS-dominant features) or ruxolitinib (for MPN-dominant features) in patients with MDS/MPN. The primary endpoint was the overall response rate (ORR) at 6 months. Twenty patients were enrolled: 4 with MDS-dominat features and 16 with MPN-dominant features. The ORR was 60% (95% CI 36.1-80.5) overall, 75% (31.1-95.4) in the MDS group, and 56.3% (33.2-76.9) in the MPN group. In the MDS group, clinical benefits included improvements in the total symptom score, erythroid response, platelet response, and spleen response (on in each of four patients; 25% for each response). In the MPN group, partial bone marrow responses occurred in three of 16 patients (18.8%), with additional benefits including spleen response (31.3%), total symptom score improvement (12.5%), erythroid response (12.5%), and platelet response (6.3%). Adverse events occurred in 14 patients (70%). Three patients experienced grade 3 of higher adverse events, including two disease-related fatalities. One patient’s disease transformed to acute myeloid leukemia. The authors conclude that selinexor combined with azacitidine or ruxolitinib showed encouraging efficacy with a manageable safety profile in patiens with MDS/MPN.